Numerous investigators have shown that declining immunologic vigor is a regular concomitant of aging. We discovered that this aspect of aging is more prominent in certain strains of mice than others and that it is accompanied by increasing autoimmunity. These changes are accelerated by thymectomy. In mice where immunologic deficiency and autoimmunity are observed during aging, preliminary evidence indicates associated thymic involution, loss of thymic dependent cells and decreased cellular medicated immune functions. The objective of our investigations is to test the relative capacities of the thymic stroma, stem cells, and immunocompetent cells of young and aging autoimmune susceptible and resistant strains to restore immune functions and prolong life in neonatally thymectomized and aging mice. Experimental models will include: 1) thymectomized mice lacking a site for differentiation of stem cells but possessing post-thymic cells, 2) thymectomized irradiated mice which lack post-thymic cells; 3) supralethally irradiated mice to test aging effects on stem cells and 4) aged mice for analysis of thymus peripheral lymphoid cells, thymus humoral influence and stem cells on the waning immune vigor. Experiments will be done to test the capacity of bone marrow cells to be differentiated by thymic stroma at different ages of autoimmune resistant and susceptible strains. Also, thymectomized mice will be treated with thymus grafts, or thymus grafts placed in millipore chambers and a small number of spleen cells from young syngeneic mice. These experiments will show that there is thymic stroma and post-thymic cell deficiency in the autoimmune susceptible strains. Thus the meaning of involution of the thymus and its system with respect to development of immune deficiency and autoimmunity with aging can be effectively assessed at the cellular level. Understanding of these relationships should ultimately help prolong useful life in man.